5EGP

Crystal structure of the S-methyltransferase TmtA

5EGP の概要

• エントリーDOI: 10.2210/pdb5egp/pdb
• 分子名称: UbiE/COQ5 family methyltransferase, putative, S-ADENOSYL-L-HOMOCYSTEINE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: bis-thiomethyltransferase, gliotoxin, epipolythiodioxopiperazine, aspergillus fumigatus, transferase
• 由来する生物種: Aspergillus fumigatus Z5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72589.76

構造登録者

Duell, E.R.,Glaser, M.,Antes, I.,Groll, M.,Huber, E.M. (登録日: 2015-10-27, 公開日: 2016-02-03, 最終更新日: 2025-12-10)

主引用文献

Duell, E.R.,Glaser, M.,Le Chapelain, C.,Antes, I.,Groll, M.,Huber, E.M.
Sequential Inactivation of Gliotoxin by the S-Methyltransferase TmtA.
Acs Chem.Biol., 11:1082-1089, 2016

PubMed Abstract: The epipolythiodioxopiperazine (ETP) gliotoxin mediates toxicity via its reactive thiol groups and thereby contributes to virulence of the human pathogenic fungus Aspergillus fumigatus. Self-intoxication of the mold is prevented either by reversible oxidation of reduced gliotoxin or by irreversible conversion to bis(methylthio)gliotoxin. The latter is produced by the S-methyltransferase TmtA and attenuates ETP biosynthesis. Here, we report the crystal structure of TmtA in complex with S-(5'-adenosyl)-l-homocysteine. TmtA features one substrate and one cofactor binding pocket per protein, and thus, bis-thiomethylation of gliotoxin occurs sequentially. Molecular docking of substrates and products into the active site of TmtA reveals that gliotoxin forms specific interactions with the protein surroundings, and free energy calculations indicate that methylation of the C10a-SH group precedes alkylation of the C3-SH site. Altogether, TmtA is well suited to selectively convert gliotoxin and to control its biosynthesis, suggesting that homologous enzymes serve to regulate the production of their toxic natural sulfur compounds in a similar manner.

PubMed: 26808594
DOI: 10.1021/acschembio.5b00905

実験手法

X-RAY DIFFRACTION (1.5 Å)